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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2021

01-02-2021 | Peritoneal Cancer | Translational Research and Biomarkers

Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer

Authors: Ann M. Miller, PhD, Caitlin D. Lemke-Miltner, PhD, Sue Blackwell, MS, Ann Tomanek-Chalkley, BS, Katherine N. Gibson-Corely, DVM, PhD, Kristen L. Coleman, PhD, George J. Weiner, MD, Carlos H. F. Chan, MD, PhD

Published in: Annals of Surgical Oncology | Issue 2/2021

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Abstract

Background

The treatment options for patients with peritoneal carcinomatosis (PC) of gastrointestinal and pancreaticobiliary origins are limited. The virus-like particle, CMP-001, composed of the Qβ bacteriophage capsid protein encapsulating a CpG-A oligodeoxynucleotide, activates plasmacytoid dendritic cells (pDCs) and triggers interferon alpha (IFNα) release, leading to a cascade of anti-tumor immune effects.

Methods

To evaluate the ability of CMP-001 to trigger an immune response in patients with PC, peritoneal cells were isolated and stimulated ex vivo with CMP-001. Both IFNα release and percentage of pDC were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. To evaluate the anti-tumor response in vivo, murine PC models were generated using mouse cancer cell lines (Panc02 and MC38) in immunocompetent mice treated with intraperitoneal CMP-001 or saline control. Survival was followed, and the immunophenotype of cells in the peritoneal tumor microenvironment was evaluated.

Results

The pDCs accounted for 1% (range 0.1–3.9%; n = 17) of the isolated peritoneal cells. Ex vivo CMP-001 stimulation of the peritoneal cells released an average of 0.77 ng/ml of IFNα (range, 0–4700 pg/ml; n = 14). The IFNα concentration was proportional to the percentage of pDCs present in the peritoneal cell mixture (r = 0.6; p = 0.037). In murine PC models, intraperitoneal CMP-001 treatment elicited an anti-tumor immune response including an increase in chemokines (RANTES and MIP-1β), pro-inflammatory cytokines (IFNγ, interleukin 6 [IL-6], and IL-12), and peritoneal/tumor immune infiltration (CD4+/CD8+ T and natural killer [NK] cells). The CMP-001 treatment improved survival in both the Panc02 (median, 35 vs 28 days) and the MC38 (median: 57 vs 35 days) PC models (p < 0.05).

Conclusions

As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.
Appendix
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Metadata
Title
Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer
Authors
Ann M. Miller, PhD
Caitlin D. Lemke-Miltner, PhD
Sue Blackwell, MS
Ann Tomanek-Chalkley, BS
Katherine N. Gibson-Corely, DVM, PhD
Kristen L. Coleman, PhD
George J. Weiner, MD
Carlos H. F. Chan, MD, PhD
Publication date
01-02-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 2/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08591-7

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